The .22 Savage Hi-Powers relatively high velocity for the time and "shocking" power led to an initial surge of popularity, and was attributed with almost magical killing powers even on large and dangerous soft-skinned game such as tigers. Reverend H. R. Caldwell used his .22 Savage Hi-Power on 400 pound tigers in China with success, something the Savage rifle company exploited in its advertising for the cartridge in the early days. The famous elephant hunter WDM Bell used a .22 Savage Hi-Power to kill Cape buffalo in West Africa in the 1920s, and reported in his magazine articles that the cartridge was popular at that time for red deer stalking in Scotland. While it was used in the UK on deer as large as Red Stags, it fell out of favour as a big game cartridge due to its small caliber and light bullets. As time went on, other .22 centerfire cartridges outstripped it in performance such as the .220 Swift, and with the advent of the .223 Remington in the 1960s, the cartridge was considered obsolete.[3] Today it is regarded as a vintage round, and aficionados use it for small game hunting in similar applications as the .223 Remington; although it is used for deer hunting where it is legal to do so. In Europe the cartridge is still chambered in drillings and similar combination guns, and the cartridge is still used by hunters for smaller European deer species such as Roe deer.

RWS 5,6x52R cartridge base

As of 2007, the .22 Savage Hi-Power is no longer made in the United States. In Europe, the .22 Savage Hi-Power is called the "5.6×52mmR", and it's still made by RWS,[4]Norma, Sellier & Bellot, and Wolf Ammunition, and exported to the U.S. market.